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Research roundup: March 2024 edition

OTC birth control pill self-selection, adherence, and interest; IUD expulsion risks; and IUD and implant side effects.

by Colleen Denny, MD and Emma Gilmore, MD

published 03/29/24

1. Evaluation of adherence to a daily progestin-only pill in a simulated over-the-counter setting

In July 2023, the US Food and Drug Administration (FDA) approved the first over-the-counter progestin-only contraceptive pill, Opill (norgestimate 0.075mg). While over-the-counter availability has the potential to reduce access barriers associated with prescription-based oral contraception, users rely solely on the product label to understand how to effectively take norgestimate pills. In this prospective study, researchers studied adherence to directions to take norgestimate pills every day at the same time among nearly 900 participants over a 24-week period. Using e-diary self-reported behavior, the researchers found that approximately 85% of all participants reported taking the pill daily on ≥85% days and taking their dose within the three-hour window on 96% of days. When accounting for patients who followed instructions correctly and used a backup method, such as condoms or abstaining from penis-in-vagina sex, for the next 48 hours when a pill was missed, 95% of participants followed label directions for more than 85% of doses. Adolescent users and users with low health literacy had similar adherence rates to the overall group. While the authors caution that aspects of the research setting may have cued or reminded patients in a way that does not reflect true OTC use patterns, this data shows similar adherence rates for OTC oral contraceptives as for prescription oral contraceptives.

2. Evaluation of consumer self-selection of a proposed over-the-counter, progestin-only daily oral contraceptive

Progestin-only contraception pills are known to be safe for almost all patients, with only one absolute contraindication, which is active breast cancer. To safely move a product from prescription to over-the-counter (OTC) access, it is important to understand whether patients can understand its labeling instructions and determine if they can safely use it. This study was conducted to understand whether consumers could make a safe determination about progestin-only pills when using the drug facts label alone. Two patient populations were assessed: a group of 1,772 all-comers, and a cohort of 206 with a suspected history of breast cancer based on diagnosis codes and prescription history. Overall, 98% of potential users were able to appropriately determine whether they could take the progestin-only pill. For the 2% who did not appropriately self-select, the vast majority were found to actually be safe to take the pill after a chart review was performed by a panel of family planning physicians. These results suggest that patients can safely navigate the appropriateness of progestin-only pills when confronted with drug fact labels, supporting the FDA approval of OTC access.

3. Interest in over-the-counter progestin-only pills among transgender, nonbinary, and gender-expansive individuals in the United States

National surveys have noted high proportions of interest in over-the-counter contraceptive pill options for adolescent and adult individuals who report their sex as female. Contraception and menstrual control are a fundamental component of gender-affirming care for transgender, non-binary, and gender-expansive individuals, but very little is known about this population’s perspective on this issue. In 2019, prior to FDA approval, the authors of this study conducted an online survey of 1,415 transgender, non-binary, and gender-expansive individuals assigned female or intersex at birth. Forty-five percent of participants expressed interest in an over-the-counter progestin-only pill, both due to the lack of estrogen in the pill and the ability to obtain it without a prescription. Given the pill’s recent FDA approval, along with changes in healthcare after COVID-19 and restrictions on care for gender-diverse individuals, interest may be even stronger today. These results suggest an opportunity for increased access to menstrual control and contraception for a frequently overlooked, marginalized patient population.

4. Relationship between long-acting reversible contraception and acne in a cohort of adolescents and young adults

Acne vulgaris is a common skin condition affecting adolescent patients and is hormonally mediated. While estrogen-progesterone contraception is known to improve acne due to its effects on ovarian androgen production and sex hormone binding globulin levels, less is known about the effect of progestin-only containing long-acting, reversible contraception (LARC), such as IUDs and the implant, on acne symptoms. In this secondary analysis of quality improvement data, the authors examined how hormonal IUD or implant use affected adolescents’ development or exacerbation of acne. Among 1,319 patients who were between 9 and 28 years old when initiating hormonal LARC, worsening acne was documented in 28.5% of patients. Of patients who had their LARC device removed, 7.4% of patients cited acne concern as a reason for removal, though only 0.92% of patients cited acne as their sole reason. The authors conclude that while the development or worsening of acne among adolescent LARC users is relatively common, it is largely manageable and rarely problematic to a level that requires LARC discontinuation.

5. Association of Intrauterine Device Malposition With Previous Cesarean Delivery and Related Uterine Anatomical Changes

Both hormonal and non-hormonal, copper IUDs provide long-acting, highly effective, and reversible contraception, and can be safely used by nulliparous patients as well as multiparous patients with a history of either vaginal or cesarean delivery. IUD malposition away from the optimal uterine fundus location, either when positioned in the lower uterus or cervix, perforated through the uterus or cervix, or rotated/inverted is uncommon. IUD malposition may be asymptomatic and detected only on imaging, but may also be associated with pelvic pain and/or decreased contraceptive efficacy. In this retrospective cohort study, the authors analyzed pelvic ultrasound records of nearly 300 patients with IUDs in place, all inserted vaginally, to determine how history of cesarean delivery (CD) affected the likelihood of IUD malposition. They determined that 19% of all IUDs appeared malpositioned, with the most common malposition in the lower uterus or cervix (68%). However, a history of CD was associated with an increased risk of IUD malposition compared to those without a CD, at 28%. Patients with a retroflexed uterus and a large cesarean scar defect were also independently associated with an increased risk of IUD malposition among patients with a history of CD. The authors discuss that clinicians who provide IUDs can consider a history of CD as a risk factor for malposition and consider changes in technique, including ultrasound guidance, to ensure the correct position at the time of placement.

6. Menstrual Cup Use and Intrauterine Device Expulsion in a Copper Intrauterine Device Randomized Trial

Non-hormonal, copper IUDs are safe for use for almost all patient populations. However, given that all IUDs are removed with gentle traction on the strings that extend into the vagina, there has been concern and conflicting data about whether menstrual cup users are at higher risks of IUD expulsion or accidental removal. In this secondary analysis of a previous trial comparing the efficacy of the TCu380A (Paragard) and NTCu380-Mini (Mona Lisa) copper IUDs, the researchers identified 250 participants who also used menstrual cups. Over 36 months, the researchers determined that menstrual cup users were more likely to have expulsions than non-cup users, but this effect was driven by a higher expulsion rate among NTCu380-Mini users (25.4%, compared to 15.1% of TCu380A cup users and 9.4% of non-cup users). Menstrual cup users were more likely than non-cup users to accidentally remove both types of IUDs, with 5.7% of TCu380A users and 10.2% of NTCu380-Mini cup users experiencing accidental self-removal over 36 months (compared to 0.9% of non-cup users). The authors advise counseling copper IUD users about the risk of accidental removal with menstrual cup use but also discuss that the rate of expulsion does not appear elevated among menstrual cup users with a TCu380A IUD, the non-hormonal IUD on the market in the US.

7. Body Mass Index and Levonorgestrel Device Expulsion in Adolescents and Young Adults

Adolescents are typically considered to be good candidates for levonorgestrel intrauterine devices (LNG IUDs). LNG IUDs are frequently offered to adolescents considering bariatric surgery, as patients are advised to avoid pregnancy for 12-18 months postoperatively, and this birth control method is not associated with increased weight gain. However, there is emerging evidence to suggest that there may be a correlation between BMI and rates of IUD expulsion. Little is known about IUD expulsion rates in the adolescent population, but this cohort is likely to consider LNG IUDs even more frequently, as rates of people with a BMI ≥ 30 mg/kg2/ and bariatric surgery increase throughout the US. To better understand expulsion rates for adolescents and young adults, the authors of this study conducted a chart review of patients aged 10-24, assigned female at birth, who received 52mg LNG IUDs at a single children’s hospital. Ultimately, the majority of charts reviewed were for patients 10-19 years old, which was the predominant age group treated at the hospital. Of 588 patients reviewed, 22.3% had a BMI ≥ 30 mg/kg2/. An increase in BMI was significantly associated with the risk of LNG IUD expulsion, and IUD placement during bariatric surgery was associated with higher odds of expulsion. The mechanism behind these increased risks is not fully understood. Further research is needed to better explore the associations noted by this study so that adolescent and young adult patients can be appropriately counseled about the risks of IUD placement.

8. Amenorrhea in Adolescents Using the Etonogestrel Contraceptive Implant

Patients who use the etonogestrel implant (Nexplanon) for contraception often experience changes in menstrual bleeding patterns, including irregular unscheduled bleeding or spotting as well as amenorrhea. There is less known about which patient features may predict the bleeding pattern patients will have with implant use, and even less known about these features in adolescent patients. In this retrospective cohort study, the authors identified 252 post-menarchal patients aged 12-22 years who had a contraceptive implant placed over four years. In examining demographic data and pre-insertion bleeding patterns, they determined that approximately 15% of patients were amenorrheic three months after insertion, and 29% were amenorrheic at 12 months. Patients who had a BMI ≥ 30 mg/kg2/, were amenorrheic at the time of insertion, had used another implant or other hormonal contraception immediately before insertion, or had developed amenorrhea by three months were all more likely to have amenorrhea at 12 months. This data can help providers prospectively counsel adolescent patients considering the contraceptive implant about possible menstrual bleeding patterns after insertion.

9. A Randomized Trial of Double Verses Single-Dose Etonogestrel Implant to Overcome the Interaction with Efavirenz-Based Antiretroviral Therapy

Efavirenz-based antiretroviral therapy is known to reduce the efficacy of the etonogestrel implant (Nexplanon), so patients receiving this treatment for HIV are typically advised to select a different birth control method. The reason is due to an accelerated degradation of the progestin in the implant. The authors of this randomized trial aimed to investigate the use of two Nexplanons, instead of one, to overcome this effect and therefore potentially have the option to place the implant in this patient population. All patients in this trial used copper intrauterine devices to prevent pregnancy and had weekly serum progesterone levels measured to track the possibility of ovulation during the study duration of 48 weeks. The authors found that having two etonogestrel implants reduced the likelihood of ovulation by more than 97% without an increase in adverse events. These results provide encouraging evidence to support the use of Nexplanon in patients using efavirenz for HIV management and warrant further exploration.

10. The risk of venous thromboembolism in oral contraceptive users: the role of genetic factors—a prospective cohort study of 240,000 women in the UK Biobank

Patients using combination pills, containing estrogen and progestin, are at an increased risk of venous thromboembolism (VTE), and this risk is further increased in patients with underlying inherited clotting disorders, such as Factor V Leiden (FVL) and prothrombin (PTM) deficiency. Typically, patients with FVL or PTM are advised not to use combination pills due to the further increased risk of blood clots. However, clinical characteristics and family history have been shown to be poor indicators of clotting risk, which makes it difficult to accurately determine VTE risk in this specific patient population. The authors of this study used polygenic risk scores, which use an individual’s genetic makeup to determine their disease risk and likely phenotype. Using the UK Biobank, they tracked almost 250,000 individuals from birth and stratified them according to their carrier status of either FVL or PTM. Their results showed that all combination pill users have an increased risk of VTE that is most pronounced during the first two years of use, and this risk is significantly higher in individuals with FVL or PTM, particularly those with higher polygenic risk scores. These results further strengthen preexisting recommendations regarding combination pills and VTE disorders, and suggest that using polygenic risk scores may provide helpful information about the interaction between genetic factors and risk for adverse events.

Colleen Denny, MD, is an attending ObGyn at Bellevue Hospital in New York City, where she is the Medical Director of the Women's Clinic, and a clinical assistant professor with the NYU School of Medicine. She enjoys providing care for patients in all phases of life and is especially interested in issues related to contraception access and public health. Outside of work, she’s a runner, a dancer, and a bit of a crossword puzzle nerd.
Emma Gilmore is a fellow in Complex Family Planning at the University of Pennsylvania. She completed her residency in Obstetrics and Gynecology at New York University. She's passionate about reproductive rights, medical education, and combating health care disparities, particularly in sexual and reproductive health. In her free time, she can be found taking her dog on walks around the beautiful parks in and around Philadelphia.
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